Forebrain-selective AMPA-receptor antagonism guided by TARP γ-8 as an antiepileptic mechanism

• Published in: Nature medicine Vol. 22; no. 12; pp. 1496 - 1501
• Main Authors: Kato, Akihiko S, Burris, Kevin D, Gardinier, Kevin M, Gernert, Douglas L, Porter, Warren J, Reel, Jon, Ding, Chunjin, Tu, Yuan, Schober, Douglas A, Lee, Matthew R, Heinz, Beverly A, Fitch, Thomas E, Gleason, Scott D, Catlow, John T, Yu, Hong, Fitzjohn, Stephen M, Pasqui, Francesca, Wang, He, Qian, Yuewei, Sher, Emanuele, Zwart, Ruud, Wafford, Keith A, Rasmussen, Kurt, Ornstein, Paul L, Isaac, John T R, Nisenbaum, Eric S, Bredt, David S, Witkin, Jeffrey M
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2016
• Subjects: 692/617/375/178; Animals; Anticonvulsants - adverse effects; Anticonvulsants - pharmacology; Benzothiazoles - pharmacology; Biomedicine; Calcium Channels - metabolism; Cancer Research; Cerebellum - drug effects; Cerebellum - metabolism; Convulsants - toxicity; Disease Models, Animal; Dizziness - chemically induced; Epilepsy - chemically induced; Epilepsy - drug therapy; Infectious Diseases; letter; Metabolic Diseases; Mice; Molecular Medicine; Neurosciences; Pentylenetetrazole - toxicity; Prosencephalon - drug effects; Prosencephalon - metabolism; Pyrazoles - pharmacology; Pyridones - adverse effects; Pyridones - pharmacology; Rats; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - metabolism; Seizures - chemically induced; Seizures - drug therapy

Selective pharmacological blockade of forebrain excitatory AMPA receptors that express the TARP γ-8 subunit enables antiepileptic therapy in rodent models of epilepsy without inducing motor impairments associated with currently used antiepileptic drugs. Pharmacological manipulation of specific neura...